Acetic Acid → HCID 59548161, compound

HRID 1812123Notes

Reaction equation

HRID 1812123 reaction equation
[CH3:1][O:2][C:3]1[CH:43]=[CH:42][C:6]([CH2:7][N:8]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:24][C:25]4[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)=[N:18][CH:19]=[C:20]([CH:23]=3)[CH:21]=O)[N:10]=2)=[CH:5][CH:4]=1.[C:44]1([CH3:50])[CH:49]=CC=CC=1.CO.[C:53]([BH3-])#[N:54].[Na+].[C:57](O)(=[O:59])C>>[CH3:41][O:40][C:37]1[CH:38]=[CH:39][C:34]([CH2:33][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:43][CH:42]=2)[C:9]2[N:10]=[C:11]([C:16]3[C:17]([NH:24][C:25]4[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)=[N:18][CH:19]=[C:20]([CH2:21][N:54]4[CH2:53][CH2:57][O:59][CH2:49][C@@H:44]4[CH3:50])[CH:23]=3)[N:12]=[C:13]([CH3:15])[N:14]=2)=[CH:35][CH:36]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 887MethanolHCID 1140TolueneHCID 5003444Sodium cyanoborohydrideHCID 601552675-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde

Product 1

HCID 59548161HCID 59548161, compoundYield 27.6%

Procedure

4 Å molecular sieves were added to a mixture of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (0.300 g, 0.519 mmol) and 3(S)-3-methylmorpholine (0.158 mL, 1.558 mmol) in toluene (50 mL, 470 mmol) and the mixture was stirred under N2 at reflux for 3 h. The mixture was filtered through Celite® (diatomaceous earth) and concentrated in vacuo to give a yellow oil. The oil was dissolved in methanol (50 mL, 1234 mmol) at 0° C. and the stirred solution was treated with sodium cyanoborohydride (0.082 mL, 1.558 mmol). Glacial acetic acid (0.500 mL, 8.66 mmol) was added slowly. The mixture was allowed to warm up to room temperature and stirred for 3 h. The reaction was quenched with 20% NaOH aqueous solution (5 mL) and water (2 mL), extracted with EtOAc and dried over K2CO3, and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (40 g) eluting with gradient of 20% to 50% EtOAc/hexane to give (S)-N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-((3-methylmorpholino)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.095 g, 0.143 mmol, 27.6% yield). m/z (ESI, +ve ion) 663.3 (M+H)+.

Workup

  1. temperatureat reflux for 3 h
  2. filtrationThe mixture was filtered through Celite® (diatomaceous earth)
  3. concentrationconcentrated in vacuo
  4. customto give a yellow oil
  5. stirringstirred for 3 h
  6. customThe reaction was quenched with 20% NaOH aqueous solution (5 mL) and water (2 mL)
  7. extractionextracted with EtOAc
  8. dry with materialdried over K2CO3
  9. concentrationconcentrated in vacuo
  10. customchromatographed through a Redi-Sep pre-packed silica gel column (40 g)
  11. washeluting with gradient of 20% to 50% EtOAc/hexane

Sources & evidence

ORD record
ord-d757b0bd72c944028e92914bb3ac7cf4
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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